Mind the Gap: What '95% Efficacy' Doesn't Tell You

— Questions on COVID vaccines and asymptomatic infection remain unsettled

by Randy Dotinga, Contributing Writer, MedPage Today February 24, 2021



If you've been listening to the news media or even some medical professionals, you might assume the FDA-authorized COVID-19 vaccines are about 95% effective at stopping you from getting infected by the virus. Think again. Despite popular belief, no one knows how well the vaccines actually perform at halting infections overall or preventing transmission. All we understand now is how well they prevent people from becoming significantly sick.


The ability of the vaccines to prevent all infections may seem like an arcane topic compared to their proven ability to stave off moderate-to-severe illness and death. Still, infection prevention "is going to be one of the determinants about how many people die. In effect, you have to vaccinate fewer people to get to herd immunity with a vaccine that protects against infection," Joshua Schiffer, MD, MSc, of Fred Hutchinson Cancer Research Center, told MedPage Today.

Why don't we know more? Because drugmakers have been focused on understanding whether vaccines prevent serious consequences of COVID-19 infection. Asymptomatic cases are secondary, even though they appear to contribute mightily to the spread of the pandemic, and they aren't being as rigorously tracked as moderate-to-severe cases.

This focus makes sense to internist Jeffrey Carson, MD, who managed the Johnson & Johnson COVID-19 vaccine trial's site at Rutgers University in New Jersey. "The logistics of doing a big trial like this are monumental," he told MedPage Today, noting that the J&J trial enrolled about 45,000 people. "Therefore, compromises are made sometimes."


It would be complicated and expensive – but not impossible – to create a vaccine trial that provides rapid data about asymptomatic cases. "You might have people swab themselves every couple days, or every week. You'll be picking up a lot of disease that way, and you'll be able to see if the vaccine prevents asymptomatic disease," Carson said.

However, that kind of trial would be very expensive, he said. Instead, vaccine makers have adopted other approaches. For example, the ongoing Novavax vaccine trial only asks participants to test themselves for COVID-19 via provided swabs if they are directed to do so after developing suspicious symptoms. I'm participating in the Novavax trial, as I reported in a previous MedPage Today article, and I haven't needed to open my packet of swabs.

We don't know much about whether COVID-19 vaccines prevent asymptomatic cases. The publicly available efficacy statistics – 94% to 95% for the FDA-authorized Moderna and Pfizer vaccines -- do not address their ability to prevent cases of COVID-19 with non-existent symptoms, although preliminary Moderna data suggest a lower likelihood of asymptomatic transmission. Additionally, a new study of the Pfizer/BioNTech vaccine in Israel indicated A close up of a Pfizer-BioNTech COVID-19 vaccine vial 92% efficacy in preventing infection -- symptomatic or not -- following the second dose.


As the New York Times helpfully explained, efficacy and effectiveness are not the same thing: "It's possible that the effectiveness of coronavirus vaccines will match their impressive efficacy in clinical trials. But if previous vaccines are any guide, effectiveness may prove somewhat lower."

Unfortunately, vaccine statistics are complicated and can be difficult for even the top minds in medicine to understand. This month, an infectious disease physician told the editors of Lancet Infectious Diseases in a letter that their editorial misunderstood what 94% to 95% efficacy means in regard to the Moderna and Pfizer vaccines and asymptomatic spread.

"It does not mean that 95% of people are protected from disease with the vaccine -- a general misconception of vaccine protection," he wrote. Instead, it "means that in a population such as the one enrolled in the trials, with a cumulated COVID-19 attack rate over a period of 3 months of about 1% without a vaccine, we would expect roughly 0.05% of vaccinated people would get diseased [with symptomatic infections]. ... Accurate description of effects is not hair-splitting; it is much-needed exactness to avoid adding confusion to an extraordinarily complicated and tense scientific and societal debate around COVID-19 vaccines."


Epidemiologist Samuel Scarpino, PhD, director of the Emergent Epidemics Lab at Northeastern University, has similar concerns about lack of insight into the effectiveness of COVID-19 vaccines. "I'm pretty confident that vaccines interrupt transmission, but we don't have data to say that. By not having a clear answer to this, we perpetuate uncertainty. And that's not good for controlling the narrative around the vaccines," he told MedPage Today.

To add to the complexity, scientists are still working to understand how vaccines affect diseases that spread from infected people who don't look or act sick. Most viral diseases, including HIV and hepatitis C, can spread from people who don't realize they're infected. "It makes a lot of sense for survival of the invaders, if you think about it. Humans who feel unwell are not going out to meet up with others, but ones who feel fine will continue along with their daily schedules, allowing the infection to spread," Bryn Boslett, MD, an infectious disease physician at the University of California San Francisco, told MedPage Today.


Scarpino and a colleague authored a 2015 report that suggested asymptomatic spread in vaccinated children may explain outbreaks of whooping cough in the U.S. and U.K. after a new vaccine was introduced. "Over 10 years, a lot of researchers across public health all over the globe have been working on this question about whether the switch in vaccines has increased the rate of asymptomatic individuals," he said.

We're not going to remain in the dark for long about asymptomatic cases of COVID-19 in vaccinated people. Vaccine trials will provide insight over time. For example, in addition to the new Israeli study, Pfizer's December report in the New England Journal of Medicine promised that "a serologic end point that can detect a history of infection regardless of whether symptoms were present (SARS-CoV-2 N-binding antibody) will be reported later."

For now, experts are urging vaccinated people to continue wearing masks and keep away from other people when possible.


"One major worry going forward is that vaccinated people will change their behavior and stop taking COVID-19 precautions," Boslett said. "It's very tempting to do so, very understandable. However, the stars are not yet aligned for us to go back to 'normal.' There is still a lot of COVID-19, and most of us are still vulnerable. We need to continue to focus on behavior to reduce new cases of COVID-19."

Last Updated February 24, 2021